This Program Project represents a joint effort among several investigations interested in the sequence of events that are precipitated by certain types of injury (sepsis, endotoxemia, etc). The end point of events in sepsis, severe trauma or burn injury is multi-organ failure which leads to death. We are convinced that systemic alteration in intermediary metabolism, humoral control and cell membrane function are some of the underlying events precipitating organ failure in patients. The overall aim of our program is to elucidate the mechanisms through which septic and traumatic challenges mediate the cellular events responsible for alterations in intermediary metabolism and host defense. The varied backgrounds, different scientific training and allegiance to several disciplines of the participating investigators create an ideal environment to successfully carry out the propose program. The program consists of two Core units and five projects. Core A lends administrative support to the research efforts of all five projects. Core B assures the production and quality control of reliable animal models, supports the needs of several projects for different types of isolated cells from the liver and other organs, and satisfies the needs of several of the projects for tissue culture related activities. Project 1 investigates the topic of "Dynamics of liver and Gut Carbohydrate Metabolism in Sepsis". Project 2 is entitled "Relationship Between the Metabolic Requirements and functional State of Mononuclear Phagocytes". Project 3 studies "Cytokine Mediation of Metabolic Adjustments to Sepsis" and Project 5 is concerned with "The Effect of Systemic Infections on Secondary Infections of the Lung". Some of the unique features of our Program include the many years of collaborative experience among the participating investigators, the variety of techniques employed by the investigators, the presence of preclinical and clinical viewpoints, investigations on several levels of organization ranging from the molecular to the whole animal, and the track record of individual productivity of the investigators in the field of sepsis and trauma. These strengths allow us to utilize recently developed ideas, information and techniques to investigate sepsis-induced metabolic alterations, through the successful coordination of physiologic, biochemical, immunologic, cellular, subcellular, molecular and pathophysiologic approaches.